Activation of Ecto-5’-nucleotidase Mediates Cardioprotection in Ischemic Preconditioning: Important Role of Protein Kinase C

When brief periods of ischemia precede sustained ischemia, infarct size is markedly limited, a phenomenon known as ischemic preconditioning.1’2 The precise mechanisms underlying this phenomenon have been investigated3’4 because identification of the primary mediator of ischemic preconditioning may contribute to the development of the potential treatment of acute myocardial infarction. Several lines of evidence suggest that beneficial effects of ischemic preconditioning are observed in the clinical settings.5’6 Recently, Liu et al7 experimentally demonstrated that an exposure to 8-sulfophenyltheophylline blunts the infarct size-limiting effect of ischemic preconditioning, and that brief periods of exposures to adenosine, instead of transient ischemia, mimic ischemic preconditioning. Thornton et al.8 showed that adenosine A1, receptors activation is responsible for the infarct size-limiting effect of ischemic preconditioning. Indeed, it has been clarified that adenosine contributes to limit infarct size.9’10 There are two different possibilities by which adenosine links with cardioprotection in ischemic preconditioning. One possibility is that release of adenosine during ischemia and reperfusion is enhanced by ischemic preconditioning, and the other possibility is that released adenosine makes myocardium resistant to ischemia and reperfusion. Here, we will discuss the possibility that ischemic preconditioning activates the enzymes responsible for adenosine release, i.e., ecto-5’-nucleotidase, and test the cause-effect relationship between activation of ecto-5’-nucleotidase and the infarct size-limiting effect in ischemic preconditioning.